2-chloro-1-(6-bromo-3,4-dihydro-1(2H)-quinolinyl)ethanone | 942035-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-chloro-1-(6-bromo-3,4-dihydro-1(2H)-quinolinyl)ethanone
• 英文别名: 1-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)-2-chloroethanone；1-(6-bromo-3,4-dihydro-2H-quinolin-1-yl)-2-chloroethanone
• CAS: 942035-74-7
• 化学式: C₁₁H₁₁BrClNO
• 分子量: 288.571
• InChiKey: JZIBWPMZELHWLB-UHFFFAOYSA-N

物化性质

• 沸点：
  465.9±45.0 °C(Predicted)
• 密度：
  1.550±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-1-(6-bromo-3,4-dihydro-1(2H)-quinolinyl)ethanone 在 硼烷四氢呋喃络合物 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 丙酮 、 乙腈 为溶剂， 反应 202.0h， 生成 2-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)-N-ethylethanamine
  参考文献：
  名称：

  1,2,3,4-Tetrahydroquinoline-Based Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: Lead Optimization Studies Resulting in the Identification of N-(1-(2-(Methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a Preclinical Development Candidate

  摘要：

  Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 (J. Med. Chem. 2011, 54, 5562-5575). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC50 = 4.7 mu M). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC50 > 30 mu M). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.

  DOI：

  10.1021/jm3000449
• 作为产物：
  描述：

  6-溴-1,2,3,4-四氢喹啉 、 氯乙酰氯 在 水 、 碳酸氢钠 作用下， 以 甲苯 、 乙酸乙酯 为溶剂， 反应 2.17h， 以84%的产率得到2-chloro-1-(6-bromo-3,4-dihydro-1(2H)-quinolinyl)ethanone
  参考文献：
  名称：

  QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY

  摘要：

  本发明涉及抑制一氧化氮合酶（NOS）的喹诺酮、四氢喹啉和相关化合物，特别是那些选择性地抑制神经型一氧化氮合酶（nNOS）而不是其他NOS同工型的化合物。本发明的NOS抑制剂，单独或与其他药用活性剂结合使用，可用于治疗或预防各种医疗状况。

  公开号：

  US20080234237A1

文献信息

• Quinolone and tetrahydroquinolone and related compounds having NOS inhibitory activity
  申请人：NeurAxon, Inc.

  公开号：US08173813B2

  公开（公告）日：2012-05-08

  The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.

  本发明涉及喹诺酮、四氢喹诺酮和相关化合物，它们抑制一氧化氮合酶（NOS），特别是选择性地抑制神经元一氧化氮合酶（nNOS）而不是其他NOS亚型。本发明的NOS抑制剂，单独或与其他药理活性剂联合使用，可用于治疗或预防各种医学疾病。
• Narrow SAR in odorant sensing Orco receptor agonists
  作者：Ian M. Romaine、Robert W. Taylor、Samsudeen P. Saidu、Kwangho Kim、Gary A. Sulikowski、Laurence J. Zwiebel、Alex G. Waterson

  DOI：10.1016/j.bmcl.2014.04.081

  日期：2014.6

  The systematic exploration of a series of triazole-based agonists of the cation channel insect odorant receptor is reported. The structure-activity relationships of independent sections of the molecules are examined. Very small changes to the compound structure were found to exert a large impact on compound activity. Optimal substitutions were combined using a 'mix-and-match' strategy to produce best-in-class compounds that are capable of potently agonizing odorant receptor activity and may form the basis for the identification of a new mode of insect behavior modification. (C) 2014 Elsevier Ltd. All rights reserved.
• Selective and antagonist-dependent µ-opioid receptor activation by the combination of 2-{[2-(6-chloro-3,4-dihydro-1(2H)-quinolinyl)-2-oxoethyl]sulfanyl}-5-phenyl-4,6-(1H,5H)-pyrimidinedione and naloxone/naltrexone
  作者：Shu-Yu Lin、Ya-Wen Tien、Yi-Yu Ke、Yung-Chiao Chang、Hsiao-Fu Chang、Li-Chin Ou、Ping-Yee Law、Jing-Hua Xi、Pao-Luh Tao、Horace H. Loh、Yu-Sheng Chao、Chuan Shih、Chiung-Tong Chen、Shiu-Hwa Yeh、Shau-Hua Ueng

  DOI：10.1016/j.bioorg.2022.105905

  日期：2022.11
• US8173813B2
  申请人：——

  公开号：US8173813B2

  公开（公告）日：2012-05-08
• [EN] QUINOLONE AND TETRAHYDROQUINOLINE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY<br/>[FR] QUINOLONES ET TÉTRAHYDROQUINOLÉINES ET COMPOSÉS APPARENTÉS AYANT UNE ACTIVITÉ INHIBITRICE DE NOS
  申请人：NEURAXON INC

  公开号：WO2008116308A1

  公开（公告）日：2008-10-02

  [EN] The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.
  [FR] La présente invention porte sur des quinolones, des tétraydroquinoléines et des composés apparentés qui inhibent l'oxyde nitrique synthase (NOS), en particulier sur celles et ceux qui inhibent de façon sélective l'oxyde nitrique synthase neuronal (nNOS) de préférence à d'autres isoformes de NOS. Les inhibiteurs de NOS de l'invention, individuellement ou en combinaison avec d'autres agents pharmaceutiquement actifs, peuvent être utilisés pour traiter ou prévenir divers états médicaux.